Strategies and Treatments for Respiratory Infections & Viral Emergencies (STRIVE): Shionogi Protease Inhibitor (Ensitrelvir)
- Conditions
- COVID-19
- Interventions
- Drug: Shionogi Protease Inhibitor (S-217622)Drug: placebo
- Registration Number
- NCT05605093
- Lead Sponsor
- University of Minnesota
- Brief Summary
Treatments are needed to improve outcomes among patients hospitalized for COVID-19, including direct-acting antiviral (DAA) agents to mitigate the pathology driven by ongoing viral replication. This trial will evaluate S-217622 (ensitrelvir), an anti-SARS-CoV2 3C-like protease inhibitor (PI) developed by Shionogi \&; Co. Ltd.
The study design is a randomized, placebo-controlled, multi-center international clinical trial that will evaluate the clinical efficacy of ensitrelvir when given in addition to standard of care (SOC) for inpatients with COVID-19. The SOC will be determined by local established guidelines and may include additional DAA (e.g., remdesivir) and immunomodulatory treatment strategies. Certain SOC treatments will be pre-specified prior to randomization.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1500
- Age ≥18 years.
- Informed consent for trial participation.
- Hospital admission (or boarding in an emergency department or other area awaiting hospital admission) with signs and/or symptoms of a respiratory infection.
- Confirmation of SARS-CoV2 infection by nucleic acid test (NAT) or equivalent non- NAT test [list of approved tests is in the PIM] collected within the prior 14 days.
- Onset of symptoms attributable to SARS-CoV2 infection occurred within 14 days before randomization.
- Hospitalized for the management of COVID-19, with signs and/or symptoms suggestive of lower respiratory tract infection.
- The patient is expected to be discharged from the hospital within the next 24 hours.
- Medical condition other than the acute respiratory infection (and its manifestations) that is likely to result in death within 7 days of randomization.
- Use of a strong CYP3A inducer within 14 days prior to enrollment
- Moribund condition, defined as prior cardiac arrest during this hospitalization and life expectancy less than 48 hours of randomization.
- Patient undergoing comfort care measures only such that treatment focuses on end-of- life symptom management over prolongation of life.
- Expected inability or unwillingness to participate in study procedures.
- In the opinion of the investigator, participation in a trial is not in the best interest of the patient.
- Allergy to investigational agent or vehicle
- Use of a concomitant medication that is contraindicated due to a drug-drug interaction with S-217622
- Moderate to severe hepatic impairment (i.e., Child-Pugh class B or C) or acute liver failure.
- Known estimated glomerular filtration rate (eGRF) <30 mL/min/1.73m 2
- Continuous renal replacement therapy or chronic dialysis
- Current pregnancy
- Current breastfeeding and unwillingness to defer breastfeeding for 30 days after the last dose of investigational agent.
- Women of child-bearing potential who are unwilling to abstain from sexual intercourse with men or practice appropriate contraception through 30 days from the last dose of the investigational agent.
- Men who are unwilling to abstain from sexual intercourse with women of child- bearing potential or to use barrier contraception through 30 days from the last dose of the investigational agent.
- Inability to take investigational agent in tablet form by mouth.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description S-217622 (ensitrelvir) plus standard of care (SOC) Shionogi Protease Inhibitor (S-217622) Study investigational agent (ensitrelvir) will be administered as oral tablets with dosing of 375mg (3 tabs) once on Day 0 and 125mg (1 tab) once daily on Days 1-4. All participants will receive the full 5-day course, including those who are discharged from hospitalization prior to Day 4. placebo plus standard of care (SOC) placebo Study investigational placebo will be administered as oral tablets with dosing of 375mg (3 tabs) once on Day 0 and 125mg (1 tab) once daily on Days 1-4. All participants will receive the full 5-day course, including those who are discharged from hospitalization prior to Day 4.
- Primary Outcome Measures
Name Time Method Days to Recovery Scale assessed over 60 days (DRS-60) 60 days post-intervention DRS-60 is a version of the STRIVE clinical recovery scale (CRS) which combines time to recovery with non-recovered clinical state and death to an ordinal outcome.0 indicates best results, 60 represents recovered on Day 60, with not recovered by Day 60 coded as 61 and death (worst outcome) as 62.
- Secondary Outcome Measures
Name Time Method mortality 60 days post-treatment proportion of participants who died by Day 60
proportion of participants who died or required new invasive mechanical ventilation 60 days post-treatment a 3-category ordinal outcome 60 days post-treatment the following categories: recovered (alive and at home at Day 60), alive and not recovered, and dead
time to recovery 60 days post-treatment
Trial Locations
- Locations (186)
Instituto Nacional de Enfermedades Respiratorias Ismael Cosió Villegas (Site 653-002)
🇲🇽Mexico City, Cdmx, Mexico
St. Vincent's Hospital (Site 612-002)
🇦🇺Sydney, New South Wales, Australia
Westmead Hospital (Site 612-058)
🇦🇺Westmead, New South Wales, Australia
Austin Health (612-020)
🇦🇺Heidelberg, Victoria, Australia
The Alfred Hospital (Site 612-017)
🇦🇺Melbourne, Victoria, Australia
Fundação Universidade Caxias do Sul Hospital Geral (649-218)
🇧🇷Caxias Do Sul, RS, Brazil
Hospital de Clínicas de Porto Alegre (649-101)
🇧🇷Porto Alegre, RS, Brazil
Sociedade Literária e Caritativa Santo Agostinho - Hospital São José (Site 649-204)
🇧🇷Criciuma, SC, Brazil
Hospital Nereu Ramos (Site 649-210)
🇧🇷Florianopolis, SC, Brazil
Unimed Joinville Cooperativa de Trabalho Médico (Site 649-202)
🇧🇷Joinville, SC, Brazil
Associação Beneficente Hospital Universitário - Universidade de Marília (Site 649-212)
🇧🇷Marília, SP, Brazil
Instituto de Infectologia Emílio Ribas - IIER (Site 649-001)
🇧🇷Sao Paulo, SP, Brazil
Real e Benemérita Associação Portuguesa de Beneficência de São Paulo (Site 649-201
🇧🇷Sao Paulo, SP, Brazil
Associação Beneficente Síria - HCor (Site 649-203)
🇧🇷Sao Paulo, SP, Brazil
Sociedade Beneficente de Senhoras Hospital Sirio-Libanês (Site 649-217)
🇧🇷Sao Paulo, SP, Brazil
Hospital Alemão Oswaldo Cruz (649-215)
🇧🇷São Paulo, SP, Brazil
Hospital SEPACO (649-207)
🇧🇷São Paulo, SP, Brazil
Aarhus Universitetshospital, Skejby (625-002)
🇩🇰Aarhus, N, Denmark
Aalborg Hospital (Site 625-005)
🇩🇰Aalborg, Denmark
Rigshospitalet, CHIP (Site 625-006)
🇩🇰Copenhagen, Denmark
Bispebjerg Hospital (Site 625-013)
🇩🇰Copenhagen, Denmark
Herlev/Gentofte Hospital (Site 625-012)
🇩🇰Hellerup, Denmark
Nordsjaellands Hospital, Hillerod (Site 625-009)
🇩🇰Hillerød, Denmark
Hvidovre University Hospital, Department of Infections Diseases (Site 625-001)
🇩🇰Hvidovre, Denmark
Kolding Sygehus, Medicinsk Afdeling (Site 625-011)
🇩🇰Kolding, Denmark
Odense University Hospital (Site 625-004)
🇩🇰Odense, Denmark
Zealand University Hospital Roskilde (Site 625-010)
🇩🇰Roskilde, Denmark
AIDS and Clinical Immunology Research Center (Site 627-201)
🇬🇪Tbilisi, Georgia
Universitätsklinikum Bonn, Medizinische Klinik I, Immunologische Ambulanz (622-010)
🇩🇪Bonn, Germany
Klinik I für Innere Medizin der Universität zu Köln (Site 622-008)
🇩🇪Cologne, Germany
Johann Wolfgang Goethe Univ. Hosp., Infektionsambulanz CRS (622-001)
🇩🇪Frankfurt, Germany
Dept of Critical Care and Pulmonary Medicine, Evangelismos General Hospital (635-020)
🇬🇷Athens, Attica, Greece
1st Respiratory Medicine Dept, Athens University Medical School (635-015)
🇬🇷Athens, Attica, Greece
3rd Dept of Medicine, Medical School (635-022)
🇬🇷Athens, Attica, Greece
Attikon University General Hospital (Site 635-009)
🇬🇷Athens, Attica, Greece
Democritus University of Thrace (635-021)
🇬🇷Alexandroupolis, Evros, Greece
Fujita Health University Hospital (Site 612-105)
🇯🇵Toyoake, Aichi, Japan
Center Hospital of the National Center for Global Health and Medicine (Site 612-101)
🇯🇵Shinjuku-Ku, Tokyo, Japan
Rinku General Medical Center (Site 612-107)
🇯🇵Osaka, Japan
Seoul National University Bundang Hospital (Site 612-904)
🇰🇷Seongnam, Gyeonggi, Korea, Republic of
Seoul St. Mary's Hospital (Site 612-903)
🇰🇷Seocho, Seoul, Korea, Republic of
Asan Medical Center (612-901)
🇰🇷Seoul, Korea, Republic of
Chung-Ang University Hospital (Site 612-902)
🇰🇷Seoul, Korea, Republic of
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (Site 653-001)
🇲🇽Mexico City, Cdmx, Mexico
University of Alabama Birmingham University Hospital (Site 213-002)
🇺🇸Birmingham, Alabama, United States
Banner University Medical Center Tucson (Site 206-004)
🇺🇸Tucson, Arizona, United States
Southern Arizona VA Healthcare System (Site 074-009)
🇺🇸Tucson, Arizona, United States
UCSF Fresno (Site 203-005)
🇺🇸Fresno, California, United States
VA Loma Linda Healthcare System (Site 074-017)
🇺🇸Loma Linda, California, United States
MemorialCare Health System (Site 066-003
🇺🇸Long Beach, California, United States
VA Long Beach Healthcare System (Site 074-026)
🇺🇸Long Beach, California, United States
Cedars-Sinai Medical Center (Site 208-002)
🇺🇸Los Angeles, California, United States
Ronald Reagan UCLA Medical Center (Site 203-002)
🇺🇸Los Angeles, California, United States
VA Northern California Health Care System (Site 074-023)
🇺🇸Mather, California, United States
Hoag Memorial Hospital Presbyterian (Site 080-026)
🇺🇸Newport Beach, California, United States
Veterans Affairs Palo Alto Health Care System (VAPAHCS) (Site 074-005)
🇺🇸Palo Alto, California, United States
UC Davis Health (Site 203-004)
🇺🇸Sacramento, California, United States
VA San Diego Healthcare System (Site 074-016)
🇺🇸San Diego, California, United States
Zuckerberg San Francisco General Hospital and Trauma Center (Site 213-007)
🇺🇸San Francisco, California, United States
UCSF Medical Center at Mount Zion (203-007)
🇺🇸San Francisco, California, United States
San Francisco VAMC (Site 074-002)
🇺🇸San Francisco, California, United States
Hospital Clínico San Carlos (Site 626-017)
🇪🇸Madrid, Spain
University of California San Francisco (Site 203-001)
🇺🇸San Francisco, California, United States
Stanford University Hospital & Clinics (Site 203-003)
🇺🇸Stanford, California, United States
Lundquist Institute for Biomedical Innovation (Site 066-002)
🇺🇸Torrance, California, United States
Rocky Mountain Regional VA Medical Center (Site 074-010)
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital (Site 204-001)
🇺🇸Aurora, Colorado, United States
Public Health Institute at Denver Health (Site 017-004)
🇺🇸Denver, Colorado, United States
Yale University (Site 025-001)
🇺🇸New Haven, Connecticut, United States
MedStar Health Research Institute/MedStar Washington Hospital Center (Site 009-021)
🇺🇸Washington, District of Columbia, United States
Washington DC VA Medical Center (Site 009-004)
🇺🇸Washington, District of Columbia, United States
University of Florida - Gainesville (Site 201-004)
🇺🇸Gainesville, Florida, United States
Miami VA Healthcare System (Site 074-003)
🇺🇸Miami, Florida, United States
Orlando VA Medical Center (Site 074-032)
🇺🇸Orlando, Florida, United States
Tampa General Hospital (032-001)
🇺🇸Tampa, Florida, United States
University of Illinois at Chicago (Site 008-012)
🇺🇸Chicago, Illinois, United States
Carle Foundation Hospital (Site 080-049)
🇺🇸Urbana, Illinois, United States
Lutheran Medical Group (Site 301-010)
🇺🇸Fort Wayne, Indiana, United States
The University of Kansas Hospital (Site 080-044)
🇺🇸Kansas City, Kansas, United States
University of Kentucky (Site 210-004)
🇺🇸Lexington, Kentucky, United States
NIH Clinical Center (Site 080-043)
🇺🇸Bethesda, Maryland, United States
Massachusetts General Hospital (202-002)
🇺🇸Boston, Massachusetts, United States
Hospital General Dr. Aurelio Valdivieso (Site 653-004)
🇲🇽Oaxaca City, OA, Mexico
Institute of Human Virology-Nigeria (IHVN) (Site 612-601)
🇳🇬Abuja, FCT, Nigeria
Hospital Nacional Hipolito Unanue (651-008)
🇵🇪Lima, Peru
Hospital Nacional Sergio E. Bernales (651-007)
🇵🇪Lima, Peru
Wojewodzki Szpital Zakazny (Site 625-302)
🇵🇱Warsaw, Poland
VA Caribbean Health Care (074-033)
🇵🇷San Juan, Puerto Rico
Tan Tock Seng Hospital (Site 612-201)
🇸🇬Singapore, Singapore
Durban International Clinical Research Site (WWH) (652-005)
🇿🇦Durban, KwaZulu-Natal, South Africa
Beth Israel Deaconess Medical Center (Site 202-001)
🇺🇸Boston, Massachusetts, United States
Baystate Medical Center (Site 201-001)
🇺🇸Springfield, Massachusetts, United States
UMass Chan Medical School (Site 080-007)
🇺🇸Worcester, Massachusetts, United States
VA Ann Arbor Healthcare System (Site 074-028)
🇺🇸Ann Arbor, Michigan, United States
Henry Ford Health System (Site 014-001)
🇺🇸Detroit, Michigan, United States
Greys Hospital (080-202)
🇿🇦Pietermaritzburg, KwaZulu-Natal, South Africa
University of Cape Town (UCT) Lung Institute (Site 080-201)
🇿🇦Cape Town, Western Cape, South Africa
Hospital Universitari Germans Trias i Pujol (626-003)
🇪🇸Badalona, Barcelona, Spain
Hospital del Mar (626-025)
🇪🇸Barcelona, Spain
Sinai-Grace Hospital (Site 205-005)
🇺🇸Detroit, Michigan, United States
Hennepin Healthcare Research Institute (Site 027-001)
🇺🇸Minneapolis, Minnesota, United States
M Health Fairview University of Minnesota Medical Center (Site 112-001)
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic (Site 054-001)
🇺🇸Rochester, Minnesota, United States
University of Mississippi Medical Center (Site 202-005)
🇺🇸Jackson, Mississippi, United States
Hospital Universitari Vall d'Hebron (Site 626-033)
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona (626-004)
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañón (Site 626-001)
🇪🇸Madrid, Spain
Hospital Universitario La Paz (Site 626-012)
🇪🇸Madrid, Spain
Washington University School of Medicine (Site 003-001)
🇺🇸Saint Louis, Missouri, United States
University of Nebraska Medical Center (Site 080-045)
🇺🇸Omaha, Nebraska, United States
Dartmouth-Hitchcock Medical Center (301-024)
🇺🇸Lebanon, New Hampshire, United States
Cooper University Hospital (Site 019-001)
🇺🇸Camden, New Jersey, United States
Hackensack Meridian Health (Site 301-030)
🇺🇸Hackensack, New Jersey, United States
New Jersey Medical School Clinical Research Center (028-001)
🇺🇸Newark, New Jersey, United States
University Hospital Zurich (Site 621-201)
🇨🇭Zurich, Switzerland
Chulalongkorn University and The HIV-NAT (Site 613-001)
🇹🇭Bangkok, Thailand
Khon Kaen University, Srinagarind Hospital (Site 613-003)
🇹🇭Khon Kaen, Thailand
MRC/UVRI & LSHTM Uganda Research Unit (634-601)
🇺🇬Entebbe, Uganda
University of New Mexico Hospital (Site 213-008)
🇺🇸Albuquerque, New Mexico, United States
CHRISTUS - St. Vincent (Site 080-051)
🇺🇸Santa Fe, New Mexico, United States
Lincoln Medical Center (Site 003-016)
🇺🇸Bronx, New York, United States
Montefiore Medical Center - Moses Hospital (Site 206-001)
🇺🇸Bronx, New York, United States
New York Presbyterian Queens (003-005)
🇺🇸Flushing, New York, United States
Mount Sinai Queens (Site 081-105)
🇺🇸Long Island City, New York, United States
St. Lawrence Health System (Site 301-029)
🇺🇸Potsdam, New York, United States
Lira Regional Referral Hospital (634-605)
🇺🇬Lira, Uganda
Masaka Regional Referral Hospital (634-606)
🇺🇬Masaka, Uganda
Treatment and Diagnostic Center ADONIS Plus (627-304)
🇺🇦Kyiv, Ukraine
Hospital #1 of Zhytomyr City Council (627-303)
🇺🇦Zhytomyr, Ukraine
Royal Free Hospital (634-006)
🇬🇧London, United Kingdom
Royal Victoria Infirmary (Site 634-007)
🇬🇧Newcastle Upon Tyne, United Kingdom
Wake Forest Baptist Health (Site 210-001)
🇺🇸Winston-Salem, North Carolina, United States
Montefiore Medical Center - Weiler campus (Site 206-003)
🇺🇸Bronx, New York, United States
James J. Peters VAMC (Site 023-003)
🇺🇸Bronx, New York, United States
St. Francis Hospital, Nsambya (Site 634-607)
🇺🇬Kampala, Uganda
NYU Long Island (301-034)
🇺🇸Mineola, New York, United States
Duke University Hospital (Site 301-006)
🇺🇸Durham, North Carolina, United States
Guy's & St. Thomas' NHS Foundation Trust (Site 634-011)
🇬🇧London, United Kingdom
NYU Brooklyn (301-033)
🇺🇸Brooklyn, New York, United States
Gulu Regional Referral Hospital (634-603)
🇺🇬Gulu, Uganda
New York University Tisch Hospital (Site 301-013)
🇺🇸New York, New York, United States
Mount Sinai Medical Center (Site 301-012)
🇺🇸New York, New York, United States
Central City Clinical Hospital of Ivano-Frankivsk City Council (Site 627-302)
🇺🇦Ivano-Frankivs'k, Ukraine
University of Cincinnati Medical Center (Site 207-003)
🇺🇸Cincinnati, Ohio, United States
Portland VA Health Care System (074-024)
🇺🇸Portland, Oregon, United States
Penn State Health Milton S. Hershey Medical Center (Site 209-002)
🇺🇸Hershey, Pennsylvania, United States
NYC Health + Hospital Harlem (Site 003-003)
🇺🇸New York, New York, United States
Weill Cornell Clinical Research Unit (065-001)
🇺🇸New York, New York, United States
Parirenyatwa General Hospital (Site 634-901)
🇿🇼Harare, Zimbabwe
Cleveland Clinic Foundation (Site 207-001)
🇺🇸Cleveland, Ohio, United States
Ohio State University Wexner Medical Center (Site 207-004)
🇺🇸Columbus, Ohio, United States
Rhode Island Hospital (Site 080-036)
🇺🇸Providence, Rhode Island, United States
The Miriam Hospital (Site 080-039)
🇺🇸Providence, Rhode Island, United States
Kent County Memorial Hospital (080-048)
🇺🇸Warwick, Rhode Island, United States
Ralph H. Johnson VA Medical Center (Site 074-015)
🇺🇸Charleston, South Carolina, United States
Medical University of South Carolina (Site 210-002)
🇺🇸Charleston, South Carolina, United States
Monument Health Rapid City Hospital (Site 213-005)
🇺🇸Rapid City, South Dakota, United States
Vanderbilt University Medical Center (Site 212-001)
🇺🇸Nashville, Tennessee, United States
Hendrick Medical Center (Site 080-014)
🇺🇸Abilene, Texas, United States
CHRISTUS Spohn Shoreline Hospital (Site 080-001)
🇺🇸Corpus Christi, Texas, United States
Baylor, Scott and White Health (301-003)
🇺🇸Dallas, Texas, United States
Parkland Health and Hospital Systems (Site 084-002)
🇺🇸Dallas, Texas, United States
UT Southwestern Medical Center (Site 084-001)
🇺🇸Dallas, Texas, United States
Houston Methodist Hospital (Site 301-028)
🇺🇸Houston, Texas, United States
MEDVAMC (Site 074-006)
🇺🇸Houston, Texas, United States
University of Texas Health Science Center (Site 203-006)
🇺🇸Houston, Texas, United States
CHRISTUS Good Shepherd Medical Center (Site 080-031)
🇺🇸Longview, Texas, United States
UT Health San Antonio (Site 009-022)
🇺🇸San Antonio, Texas, United States
Intermountain Medical Center (Site 211-001)
🇺🇸Murray, Utah, United States
University of Utah Health (Site 211-002)
🇺🇸Salt Lake City, Utah, United States
University of Virginia Health System, University Hospital (Site 210-003)
🇺🇸Charlottesville, Virginia, United States
Salem VA Medical Center (Site 074-014)
🇺🇸Salem, Virginia, United States
Harborview Medical Center (208-001)
🇺🇸Seattle, Washington, United States
Providence (Sacred Heart) (Site 213-004)
🇺🇸Spokane, Washington, United States
West Virginia University Medicine
🇺🇸Morgantown, West Virginia, United States
William S. Middleton Memorial Veterans Hospital (074-030)
🇺🇸Madison, Wisconsin, United States
Froedtert Memorial Lutheran Hospital (052-001)
🇺🇸Milwaukee, Wisconsin, United States
Instituto Medico Platense (Site 611-025)
🇦🇷La Plata, Buenos Aires, Argentina
Sanatorio Allende (Site 611-030)
🇦🇷Córdoba, Cordoba, Argentina
Clínica Central S.A. (611-028)
🇦🇷Villa Regina, Rio Negro, Argentina
Sanatorio Británico S.A. (611-027)
🇦🇷Rosario, Santa Fe, Argentina
CEMIC (Site 611-021)
🇦🇷Buenos Aires, Argentina
Hospital Rawson (Site 611-012)
🇦🇷Cordoba, Argentina
Sanatorio Medico de Diagnostico y Tratamiento (611-029)
🇦🇷Santa Fe, Argentina
South Western Sydney Local Health District, Liverpool (Site 612-063)
🇦🇺Liverpool, New South Wales, Australia